Children’s views on postsurgical pain in recovery units in Norway: A qualitative study

Aims and objectives: To explore children’s postsurgical experiences with pain and pain management in the recovery unit. Background: Children’s pain is underestimated and undertreated. Untreated pain can cause unnecessary suffering, increased complication risks, and may lead to chronic pain. Research exploring children’s experiences with postoperative pain and pain management is limited. Design: A qualitative, exploratory study. The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ). Methods: Children (N=20), 8–16 years old, took part in semi-structured interviews about their experiences with pain and postoperative pain management while they were in a recovery unit. Data were collected at two university hospitals in Norway. Content analysis was used to analyse the data. Results: Three themes emerged from the interviews; “children’s experiences of what felt unpleasant and painful”, “children’s experiences with pain management” and “children’s recommendations for future pain management”. About half of the children reported moderate to severe pain while in the recovery unit and they did not always tell their nurses when they had pain. They also reported experiencing pain in places other than their surgical wounds and stated that nausea and vomiting felt unpleasant and painful. The children indicated that pain medications and the use of non-pharmacological methods helped them cope with their pain and provided several recommendations about how to improve pain management. Conclusion: Paediatric postoperative pain management remains suboptimal. The children in our study provided useful information about their pain experiences, how to improve pain management and explained why they did not tell their nurses when they were in pain. Relevance to clinical practice: These findings should direct further improvements in paediatric postoperative pain management, such as increased use of pain assessment tools and preparatory information, as well as more appropriate administration of pain medications. This is the peer reviewed version of the following article: Twycross, A.M., Smeland, A., Torgun, N., Nybro, L., Rustøen, T., Lundberg, S., and Reinertsen, H. (2019). Children’s views on postsurgical pain in recovery units in Norway: A qualitative study. Journal of Clinical Nursing, which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1111/jocn.14788. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation.

Accumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. Here we introduce a statistical tool, MiXeR, which quantifies polygenic overlap irrespective of genetic correlation, using GWAS summary statistics. MiXeR results are presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that 8.3 K variants causally influence schizophrenia and 6.4 K influence bipolar disorder. Among these variants, 6.2 K are shared between the disorders, which have a high genetic correlation. Further, MiXeR uncovers polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, the phenotypes share 8.3 K causal variants, while 2.5 K additional variants influence only educational attainment. By considering the polygenicity, discoverability and heritability of complex phenotypes, MiXeR analysis may improve our understanding of cross-trait genetic architectures

Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma: 63 patients with a minimum follow-up of 4 years

Background and purpose The Scandinavian Sarcoma Group (SSG) XIV protocol is based on experience from previous SSG trials and other osteosarcoma intergroup trials, and has been considered the best standard of care for patients with extremity localized, non-metastatic osteosarcoma. We analyzed the outcome in 63 consecutive patients. Patients and methods From 2001 through 2005, 63 patients recruited from centers in Sweden, Norway, and Finland were included. They received preoperative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m(2)), cisplatin (90 mg/m(2)), and doxorubicin (75 mg/m(2)). 3 cycles were administered post-operatively, and poor histological responders were given 3 additional cycles of ifosfamide (10-12 g/m(2)) as a salvage strategy. Results With a median follow-up of 77 months for survivors, the estimated metastasis-free and sarcoma-related survival at 5 years was 70% and 76%, respectively. 53 patients were treated with limb salvage surgery or rotationplasty and 2 patients experienced a local recurrence. 3 toxic deaths were recorded, all related to acute toxicity from chemotherapy. The 5-year metastasis-free survival of poor histological responders receiving add-on treatment with ifosfamide was 47%, as compared to 89% for good histological responders. Interpretation Outcome from the SSG XIV protocol compares favorably with the results of previous SSG trials and other published osteosarcoma trials. However, salvage therapy given to poor responders did not improve outcome to a similar degree as for good responders. In a multi-institutional setting, more than four-fifths of the patients were operated with limb salvage surgery or rotationplasty, with few local recurrences

Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 cohort

BACKGROUND: High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. EURAMOS-1 is a collaboration of four study groups aiming to improve outcomes in this rare disease by facilitating the conduct of randomised controlled trials. METHODS: Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma where complete surgical resection at all sites was deemed possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between Apr-2005 and Jun-2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients. RESULTS: For all registered patients at a median follow-up of 54 months (IQR: 38-73) from biopsy, 3-year and 5-year event-free survival were 59% (95%CI 57%-61%) and 54% (95%CI 52%-56%) respectively. Multivariate analyses showed the most adverse factors at diagnosis were pulmonary metastases (HR=2.34, 95%CI 1.95-2.81), non-pulmonary metastases (HR=1.94, 95%CI 1.38-2.73) or an axial skeleton tumour site (HR=1.53, 95%CI 1.10-2.13). The histological subtypes telangiectatic (HR=0.52, 95%CI 0.33-0.80) and unspecified conventional (HR=0.67, 95%CI 0.52-0.88) were associated with a favourable prognosis compared to chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95%CI 77%-81%) and 71% (95%CI 68%-73%) respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR=2.13, 95%CI 1.76-2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. CONCLUSIONS: In conclusion, data from > 2,000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified as at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and due to the large numbers of patients registered, sheds light on some additional factors to consider

Identification of nucleolar protein No55 as a tumour-associated autoantigen in patients with prostate cancer

Four different genes were identified by immunoscreening of a cDNA expression library from the human prostate cancer cell line DU145 with allogeneic sera from four prostate cancer patients. A cDNA encoding the nucleolar protein No55 was further analysed and shown to be expressed at the mRNA level in several normal tissues, including ovaries, pancreas and prostate and in human prostate cancer cell lines PC-3, PC-3m and LNCaP. By reverse transcriptase/polymerase chain reaction, expression of No55 was several-fold higher in two out of nine prostate cancer primary tumours and two out of two metastatic lesions, compared to normal prostate tissue. Antibodies to No55 were detected in sera from seven out of 47 prostate cancer patients but not in sera from 20 healthy male controls. Sequence analysis of the No55 open reading frame from normal and tumour tissues revealed no tumour-specific mutations. The No55 gene was located to chromosome 17q21, a region reported to be partially deleted in prostate cancer. Considering the immunogenicity of the No55 protein in the tumour host, the expression profile and chromosomal localization of the corresponding gene, studies evaluating No55 as a potential antigen for immunological studies in prostate cancer may be warranted. © 2000 Cancer Research Campaig

Biochemical analysis of novel NAA10 variants suggests distinct pathogenic mechanisms involving impaired protein N-terminal acetylation

NAA10 is the catalytic subunit of the N-terminal acetyltransferase complex, NatA, which is responsible for N-terminal acetylation of nearly half the human proteome. Since 2011, at least 21 different NAA10 missense variants have been reported as pathogenic in humans. The clinical features associated with this X-linked condition vary, but commonly described features include developmental delay, intellectual disability, cardiac anomalies, brain abnormalities, facial dysmorphism and/or visual impairment. Here, we present eight individuals from five families with five different de novo or inherited NAA10 variants. In order to determine their pathogenicity, we have performed biochemical characterisation of the four novel variants c.16G>C p.(A6P), c.235C>T p.(R79C), c.386A>C p.(Q129P) and c.469G>A p.(E157K). Additionally, we clinically describe one new case with a previously identified pathogenic variant, c.384T>G p.(F128L). Our study provides important insight into how different NAA10 missense variants impact distinct biochemical functions of NAA10 involving the ability of NAA10 to perform N-terminal acetylation. These investigations may partially explain the phenotypic variability in affected individuals and emphasise the complexity of the cellular pathways downstream of NAA10.publishedVersio